IND-Enabling Toxicology for Advanced Therapeutics

A standardized toxicology template does not exist for advanced therapeutics and complex biologics. Applying proven intelligence in IND-enabling toxicology is how we accelerate programs, designing data-driven safety studies tailored to the specific modality, from AAV vectors to LNP/RNA systems. Our approach moves beyond simple templates to build a comprehensive safety profile that withstands regulatory scrutiny from agencies including the FDA, EMA/MHRA, and other global regulatory bodies.

Designing Data-Driven Safety Studies

A preclinical program must be designed to accurately inform clinical risk. This requires a deep understanding of the biological activity of the therapeutic agent, potential off-target effects, and the host immune response.

Comprehensive IND-Enabling Capabilities

Our IND-enabling toxicology capabilities include:

• Systemic exposure and tolerability evaluations
• GLP-compliant toxicology and safety pharmacology studies
• Comprehensive biodistribution and vector shedding analysis
• Full-service pathology and histopathology review
• Immunotoxicology and immunogenicity assessments

A Rigorous Approach to Translatability and Animal Welfare

Once you’ve made a discovery, it has to be tested in life. The challenge becomes transitioning from a very controlled environment to an uncontrolled environment, which introduces a completely different biological language. This transition is where a scientifically rigorous toxicology program becomes the primary determinant of success. For many genetic therapies, this requires preclinical models with an immune system that closely mirrors human biology to generate translatable data.

Executing these complex studies correctly is a scientific and ethical obligation. We ensure that studies are done right the first time, rigorously avoiding the unnecessary use of animal models through optimized, efficient study designs. This principle guides our strategy, ensuring maximum data acquisition from each phase while strictly adhering to international welfare guidelines.

Tailoring Preclinical Models for Vector Diversity

The selection of the AAV serotype is a critical variable that directly influences tissue tropism, transduction efficiency, and potential safety liabilities. While the ongoing development of novel recombinant AAV vectors provides an expanding toolkit for targeted gene delivery, high-dose administrations can trigger severe, vector-induced toxicities in translational models such as Non-Human Primates (NHP) (PMID: 29378426).

Because each unique serotype presents a distinct biodistribution and immunogenic profile, a rigid template cannot be applied. Our study directors work directly with sponsor teams to design tailored safety evaluations, carefully aligning the preclinical model with the specific vector chosen to ensure the generated data is highly predictive and translatable.

Our programs are supported by phase-appropriate bioanalytical assay development, including under GLP guidelines as appropriate, providing reliable data on vector kinetics, transgene expression, and immune responses.